The balance of proliferation and differentiation in stem and progenitor cell populations must meet organismal needs. However, molecular mechanisms that mediate this balance are poorly understood. For germ cells, this correlation is particularly vital since the failure to produce sufficient germ cell progenitors is deleterious for fertility. We recently discovered that the environment can influence on germ cell development via sensory modalities that act through neurons. We found that TGF? signaling influences the stem cell proliferation versus differentiation decision in the C. elegans germ line at a critical time when it is expanding its stem cell pool. We found that DAF- 7/TGF? exerts its effects on the germ line in response to specific sensory cues and through two specific neurons that report the favorability of the environment. We also found that the TGF? receptor pathway acts in the germline stem cell niche, not the germ line. TGF? signaling thereby couples fertility to the quality of the environment by acting through the stem cell niche. In this proposal we address the regulation of the TGF? in response to the environment, and mechanisms downstream of the TGF? receptor that ultimately transmit information to the germ line. PUBLIC HEALTH RELEVANCE: Environmental factors impact reproduction. This application follows from our surprising discovery that the environment can influence fertility by way of chemosensory neurons and a conserved TGF? signaling pathway in C. elegans. Our studies will likely benefit human health since the cellular and molecular mechanisms underlying these controls are evolutionarily conserved.